P-0185 - Combined administration of 5-fluorouracil as well as 2-oxohexyl isothiocyanate with selol gives synergistic toxic effect on HT -29 colorectal cancer...

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Basic Science
Colon Cancer
Rectal Cancer
Presenter Lidia Śliwka
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors S. Mielczarek, A. Gilbert, A. Flis, P. Suchocki
  • Medical University, Warsaw/PL

Abstract

Introduction

Selol is the original Polish patented discovery. It is an organic selenium compound in oxidation state of +4. Currently Selol is a subject of intensive research that suggests the possibility of its use in the therapy of cancer [1,2,3]. For this reason, we investigated the effect of combined use of Selol and 5 -fluorouracil (5- FU). 5- FU is chemotherapeutic agent commonly used in the treatment of colorectal cancer. Numerous studies have also shown that ITC potentiate action of cytotoxic compounds used in antitumor therapy [4,5]. ITCs are low-molecular compounds that are present in significant quantity in vegetables of the family Brassicaceae. They are widely recognized to have chemopreventive activity [6].

Methods

Combination of Selol with 5-FU as well as with ITC cell was administered to HT-29 colon adenocarcinoma cell line. Selol's and 5 –FU's toxicity was assessed after administration separately and in combination. We also examined the influence of well known ITC - sulforaphane (SFN) and its new, patented analogs: alyssin, 2-oxohexyl ITC and 2 – oxohepytl ITC on Selol's antiproliferative properties. Cell lines were incubated for 72h with either Selol and 5- FU or Selol and ITC as well as with separate compounds. Next, MTT cytotoxicity assay was performed to evaluate antiproliferative activity. Basing on the results obtained, IC50 values of tested compounds were calculated in the program CalcuSyn. The calculations were used in the interaction studies using the Chou – Talalay's method [7].

Results

The study allowed to emerge beneficial combinations of compounds. Combined administration of Selol and 5-FU in the treatment of colorectal cancer results in a stronger cytotoxic effect than monotherapy. And it applies to both compounds (synergistic interaction). This can allow more than two - fold decrease of dose of studied compounds. The evaluation of combination of Selol and ITCs showed that 2 - oksohexyl ITC is the strongest enhancer of Selol. The combined use of those two can result in use of lower doses of both compounds.

Conclusion

Combined use of Selol and 5-FU, as well as Selol and 2-oksoheksyl ITC potentiate toxic activity of these compounds on HT-29 cell line.